Personal Blog # 28 … Lecanemab … Promising New Effective AD Medication, or Just another Disappointment? … 10/4/22

 According to an article in The Washington Post on 9/27/22, “An experimental Alzheimer’s drug (Lecanemab) slowed cognitive and functional decline by 27 percent in a closely watched clinical trial.  Japanese drugmaker Eisai and its American partner, Biogen, said the slowing of deterioration, compared with a placebo, was “highly statistically significant.”

The Phase 3 clinical trial, called Clarity AD, had1795 participants with mild cognitive impairment caused by Alzheimer’s or early-stage Alzheimer’s and “demonstrated that lecanemab reduces abnormal clumps of beta amyloid, a hallmark of Alzheimer’s.”  The article went on to say that “Eisai, which is taking the lead in developing the drug and working with regulatory authorities, will present the full results of the study in late November at an Alzheimer’s conference in San Francisco. The results also will be published in a medical journal.”

 

As of today, there has been neither peer review nor publication of the results reported.

 

“Officials said the clinical trial participants were tested in several areas to gauge the pace of their decline, including memory, orientation and problem solving.  Starting at six months, the companies said, the group that received the treatment did better than the placebo group. The treatment was administered intravenously twice a month.

The lecanemab group experienced side effects including brain swelling and bleeding — complications of anti-amyloid therapies — but the rates were within expectations, the companies said in the release.” 

 

That range of serious adverse side effects, not reported in this Post article but available on the Biogen website, noted that 17% of the patients taking this medication suffered cerebral micro and macro hemorrhages and superficial siderosis compared to 8.7% in the placebo group.  (See posting on Biogen website entitled, “Lecanemab Confirmatory Phase 3 Clarity AD Study Met Primary Endpoint …” 9/27/22.)

 

Until this clinical trial data undergoes peer review, we can only hope that despite almost double the rate of serious negative outcomes, this medication may prove to be helpful for some patients with MCI or those in early stages of AD.  Sadly, too often in the past there have been early claims made about favorable outcomes with proposed new AD medication that did not stand up to scientific scrutiny.  Also, some studies have yielded “statistically significant” results on tests that did not really make much difference in the “real world” lives of those with AD … test results that were statistically significant but not clinically significant.

 

As a former 24/7 AD spouse caregiver, I often think of “statistically significant” AD test results in this way:  Suppose one has 2000 equally healthy and robust house plants, each having 100 healthy leaves, with each plant expected to live for one full year before losing all of its healthy leaves.  A clinical trial is conducted to test whether or not a chemical added to “enrich” the water is better than just plain water for these plants.  For the next year, 1000 plants receive regular water and 1000 plants receive the “enriched” water.  After one year, the plants receiving enriched water have 96 or more dead leaves, while the plants receiving only regular water have 98 or more dead leaves.  If that study then concluded that the difference in dead leaves is statistically significant, those results would be totally meaningless to me.  The bottom line is one would have two dead plants!  The plant with “only” 96 dead leaves would not look appreciably healthier than the plant with 98 dead leaves. 

 

In other words, there is “statistical” significance and there is “clinical” difference.  I am hoping for the day when a new AD medication will prove clinically effective in the “real world,” meaning that there will be a positive consequential difference in the lives of those with AD … a much longer time before symptoms develop or worsen, or complete disappearance of some symptoms, let alone cure this horrible disease.

 

Until the clinical trial data on lecanemab is subject to peer review and critically examined to demonstrate that there are meaningful positive differences in the lives of clinical trial participants who took this medication, I won’t let myself get too excited.  Not just yet.  I have been disappointed too many times.  I have seen too many dead plants.